A Tetrahymena Piwi Bound to Mature tRNA 3′ Fragments Activates the Exonuclease Xrn2 for RNA Processing in the Nucleus

SummaryEmerging evidence suggests that Argonaute (Ago)/Piwi proteins have diverse functions in the nucleus and cytoplasm, but the molecular mechanisms employed in the nucleus remain poorly defined. The Tetrahymena thermophila Ago/Piwi protein Twi12 is essential for growth and functions in the nucleus. Twi12-bound small RNAs (sRNAs) are 3′ tRNA fragments that contain modified bases and thus are attenuated for base pairing to targets. We show that Twi12 assembles an unexpected complex with the nuclear exonuclease Xrn2. Twi12 functions to stabilize and localize Xrn2, as well as to stimulate its exonuclease activity. Twi12 function depends on sRNA binding, which is required for its nuclear import. Depletion of Twi12 or Xrn2 induces a cellular ribosomal RNA processing defect known to result from limiting Xrn2 activity in other organisms. Our findings suggest a role for an Ago/Piwi protein and 3′ tRNA fragments in nuclear RNA metabolism.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (338 K)Download as PowerPoint slideHighlights► Twi12, an essential Piwi protein, forms a stable nuclear complex with the exonuclease Xrn2 ► Twi12 is required for Xrn2 cellular accumulation, localization, and activity ► Twi12 nuclear localization requires tRNA-derived small RNA binding ► The Twi12-Xrn2 complex mediates ribosomal RNA processing